Does intranasal dexmedetomidine provide adequate plasma concentrations for sedation in children: a pharmacokinetic study.

BACKGROUND: Atomised intranasal dexmedetomidine administration is an attractive option when sedation is required for paediatric diagnostic procedures, as vascular access is not required. The risk of haemodynamic instability caused by dexmedetomidine necessitates better understanding of its pharmacokinetics in young children. To date, intranasal dexmedetomidine pharmacokinetics has only been studied in adults. METHODS: Eighteen paediatric patients received dexmedetomidine 1 or 2 µg kg-1 intranasally or 1 µg kg-1 i.v. Plasma concentrations were determined by liquid chromatography/mass spectrometry. Non-compartmental analysis provided estimates of Cmax and Tmax. Volume of distribution, clearance, and bioavailability were estimated by simultaneous population PK analysis of data after intranasal and i.v. administration. Dexmedetomidine plasma concentration-time profiles were evaluated by simulation for intranasal and i.v. administration. RESULTS: An average peak plasma concentration of 199 pg ml-1 was achieved 46 min after 1 µg kg-1 dosing and 355 pg ml-1 was achieved 47 min after 2 µg kg-1 dosing. A two-compartment pharmacokinetic model, with allometrically scaled parameters, adequately described the data. Typical bioavailability was 83.8% (95% confidence interval 69.5-98.1%). CONCLUSION: Mean arterial plasma concentrations of dexmedetomidine in infants and toddlers approached 100 pg ml-1, the low end reported for sedative efficacy, within 20 min of an atomised intranasal administration of 1 µg kg-1. Doubling the dose to 2 µg kg-1 reached this plasma concentration within 10 min and achieved almost twice the peak concentration. Peak plasma concentrations with both doses were reached within 47 min of intranasal administration, with an overall bioavailability of 84%.

Comparative usability of modern anaesthesia ventilators: a human factors study.

BACKGROUND: The anaesthesia ventilator represents the key equipment for intraoperative respiratory care. Improper operation of this device may threaten a patient's health. A self-explanatory interface facilitates handling and decreases the risk of operating errors. This study systematically evaluates the usability of user interfaces in four modern anaesthesia ventilators. METHODS: Twenty naïve operators were asked to execute 20 tasks on each of four different anaesthesia ventilators (Avance CS2™, GE Healthcare; Flow-i™, Maquet; and Perseus™ and Primus™, Dräger) in a randomized order. The success of task execution, frequency of requests for assistance, and processing times were recorded. During the tasks, the operators' visual focus was measured via eye-tracking. Additionally, subjective assessments of usability were evaluated by a standardized questionnaire. For comparison, six experienced operators undertook the same protocol. RESULTS: The overall rate of falsely executed tasks was low. Naïve operators requested assistance least when using the Perseus (26). Pooled processing times were shortest for the Perseus (222 s), followed by the Primus (223 s), the Avance (238 s), and the Flow-i (353 s). Task-specific processing times differed considerably between the devices. Eye-tracking analyses revealed associated interface issues that impeded the operators' performance. Operators rated usability best for the Perseus [mean (sd): 67 (17) arbitrary units] and worst for the Flow-i [50 (16) arbitrary units]. Results from experienced operators support these findings by trend. CONCLUSIONS: The usability of modern anaesthesia ventilators differs considerably. Interface issues of specific tasks impair the operator's efficiency. Eliminating the specific usability issues might improve the operator's performance and, as a consequence, the patient's safety.

Impact of Pdx1-associated chromatin modifiers on islet ß-cells.

Diabetes mellitus arises from insufficient insulin secretion from pancreatic islet ß-cells. In type 2 diabetes (T2D), ß-cell dysfunction is associated with inactivation and/or loss of transcription factor (TF) activity, including Pdx1. Notably, this particular TF is viewed as a master regulator of pancreas development and islet ß-cell formation, identity and function. TFs, like Pdx1, recruit coregulators to transduce activating and/or repressing signals to the general transcriptional machinery for controlling gene expression, including modifiers of DNA, histones and nucleosome architecture. These coregulators impart a secondary layer of control that can be exploited to modulate TF activity. In this review, we describe Pdx1-recruited coregulators that impact chromatin structure, consequently influencing normal ß-cell function and likely Pdx1 activity in pathophysiological settings.

Increasing positive end-expiratory pressure (re-)improves intraoperative respiratory mechanics and lung ventilation after prone positioning.

BACKGROUND: Turning a patient prone, changes the respiratory mechanics and potentially the level of positive end-expiratory pressure (PEEP) that is necessary to prevent alveolar collapse. In this prospective clinical study we examined the impact of PEEP on the intratidal respiratory mechanics and regional lung aeration in the prone position. We hypothesized that a higher PEEP is required to maintain compliance and regional ventilation in the prone position. METHODS: After ethical approval, 45 patients with healthy lungs undergoing lumbar spine surgery were examined in the supine position at PEEP 6 cm H2O and in the prone position at PEEP (6, 9 and 12 cm H2O). Dynamic compliance (CRS) and intratidal compliance-volume curves were determined and regional ventilation was measured using electrical impedance tomography. The compliance-volume curves were classified to indicate intratidal derecruitment, overdistension, or neither. RESULTS: CRS did not differ between postures and PEEP levels (P>0.28). At a PEEP of 6 cm H2O a compliance-volume profile indicating neither derecruitment nor overdistension was observed in 38 supine, but only in 20 prone positioned patients (P<0.001). The latter increased to 33 and 37 (both P<0.001) when increasing PEEP to 9 and 12 cm H2O, respectively. Increasing PEEP from 6 to 9 cm H2O in the prone position increased peripheral ventilation significantly. CONCLUSIONS: Respiratory system mechanics change substantially between supine and prone posture, which is not demonstrated in routine measurements. The intratidal compliance analysis suggests that in most patients a PEEP above commonly used settings is necessary to avoid alveolar collapse in the prone position. CLINICAL TRIAL REGISTRATION: DRKS 00005692.

Double-lumen tubes and auto-PEEP during one-lung ventilation.

BACKGROUND: Double-lumen tubes (DLT) are routinely used to enable one-lung-ventilation (OLV) during thoracic anaesthesia. The flow-dependent resistance of the DLT's bronchial limb may be high as a result of its narrow inner diameter and length, and thus potentially contribute to an unintended increase in positive end-expiratory pressure (auto-PEEP). We therefore studied the impact of adult sized DLTs on the dynamic auto-PEEP during OLV. METHODS: In this prospective clinical study, dynamic auto-PEEP was determined in 72 patients undergoing thoracic surgery, with right- and left-sided DLTs of various sizes. During OLV, air trapping was provoked by increasing inspiration to expiration ratio from 1:2 to 2:1 (five steps). Based on measured flow rate, airway pressure (Paw) and bronchial pressure (Pbronch), the pressure gradient across the DLT (ΔPDLT) and the total auto-PEEP in the respiratory system (i.e. the lungs, the DLT and the ventilator circuit) were determined. Subsequently the DLT's share in total auto-PEEP was calculated. RESULTS: ΔPDLT was 2.3 (0.7) cm H2O over the entire breathing cycle. At the shortest expiratory time the mean total auto-PEEP was 2.9 (1.5) cm H2O (range 0-5.9 cm H2O). The DLT caused 27 to 31% of the total auto-PEEP. Size and side of the DLT's bronchial limb did not impact auto-PEEP significantly. CONCLUSIONS: Although the DLT contributes to the overall auto-PEEP, its contribution is small and independent of size and side of the DLT's bronchial limb. The choice of DLT does not influence the risk of auto-PEEP during OLV to a clinically relevant extent. CLINICAL TRIAL REGISTRATION: DRKS00005648.

Intraoperative compliance profiles and regional lung ventilation improve with increasing positive end-expiratory pressure.

BACKGROUND: Anaesthesia and mechanical ventilation can lead to impaired lung. Intraoperative positive end-expiratory pressure (PEEP) should prevent intratidal recruitment/derecruitment without causing overdistension. The intratidal compliance profile indicates both unwanted phenomena. We hypothesized that a higher than usual PEEP improves the intratidal compliance and the regional lung ventilation of patients with healthy lungs. METHODS: After ethics approval, 30 adult patients scheduled for limb surgery were investigated at PEEP 5, 7 and 9 cm H2 O during mechanical ventilation. We calculated the dynamic compliance of the respiratory system (CRS ) and the intratidal volume-dependent CRS curve. The CRS curve indicated intratidal recruitment/derecruitment and/or overdistension. Regional ventilation was measured using electrical impedance tomography. RESULTS: At PEEP 5, 7 and 9 cm H2 O, intratidal recruitment/derecruitment was observed in 92%, 84% and 46% (P < 0.05) of the patients respectively. Increasing PEEP was associated with recruitment in the dorsal regions of the lungs (P < 0.001). At PEEP 9 cm H2 O, lung overdistension was indicated in two patients. With PEEP levels up to 9 cm H2 O, no significant effects on haemodynamic variables were found. CONCLUSION: We conclude that in most patients, the often applied PEEP of 5 cm H2 O is insufficient to prevent intratidal recruitment/derecruitment and that few patients show overdistension at high PEEP levels. To establish optimal pressure-volume relationships in the respiratory system, the analysis of the individual intratidal compliance profiles could be a means for individualized perioperative PEEP titration.

Intraoperative positive end-expiratory pressure evaluation using the intratidal compliance-volume profile.

BACKGROUND: Lung-protective mechanical ventilation during general surgery including the application of PEEP can reduce postoperative pulmonary complications. In a prospective clinical observation study, we evaluated volume-dependent respiratory system compliance in adult patients undergoing ear-nose-throat surgery with ventilation settings chosen empirically by the attending anaesthetist. METHODS: In 40 patients, we measured the respiratory variables during intraoperative mechanical ventilation. All measurements were subdivided into 5 min intervals. Dynamic compliance (CRS) and the intratidal volume-dependent CRS curve was calculated for each interval and classified into one of the six specific compliance profiles indicating intratidal recruitment/derecruitment, overdistension or all. We retrospectively compared the occurrences of the respective compliance profiles at PEEP levels of 5 cm H2O and at higher levels. RESULTS: The attending anaesthetists set the PEEP level initially to 5 cm H2O in 29 patients (83%), to 7 cm H2O in 5 patients (14%), and to 8 cm H2O in 2 patients (6%). Across all measurements the mean CRS was 61 (11) ml cm H2O(-1) (40-86 ml cm H2O(-1)) and decreased continuously during the procedure. At PEEP of 5 cm H2O the compliance profile indicating strong intratidal recruitment/derecruitment occurred more often (18.6%) compared with higher PEEP levels (5.5%, P<0.01). Overdistension was practically never observed. CONCLUSIONS: In most patients, a PEEP of 5 cm H2O during intraoperative mechanical ventilation is too low to prevent intratidal recruitment/derecruitment. The analysis of the intratidal compliance profile provides the rationale to individually titrate a PEEP level that stabilizes the alveolar recruitment status of the lung during intraoperative mechanical ventilation. TRIAL REGISTRATION NUMBER: DRKS00004286.

A Model-Based Product Evaluation Protocol for Comparison of Safety-Engineered Protection Mechanisms of Winged Blood Collection Needles.

OBJECTIVE: To evaluate differences in product characteristics and user preferences of safety-engineered protection mechanisms of winged blood collection needles. DESIGN: Randomized model-based simulation study. SETTING: University medical center. PARTICIPANTS: A total of 33 third-year medical students. METHODS: Venipuncture was performed using winged blood collection needles with 4 different safety mechanisms: (a) Venofix Safety, (b) BD Vacutainer Push Button, (c) Safety-Multifly, and (d) Surshield Surflo. Each needle type was used in 3 consecutive tries: there was an uninstructed first handling, then instructions were given according to the operating manual; subsequently, a first trial and second trial were conducted. Study end points included successful activation, activation time, single-handed activation, correct activation, possible risk of needlestick injury, possibility of deactivation, and preferred safety mechanism. RESULTS: The overall successful activation rate during the second trial was equal for all 4 devices (94%-100%). Median activation time was (a) 7 s, (b) 2 s, (c) 9 s, and (d) 7 s. Single-handed activation during the second trial was (a) 18%, (b) 82%, (c) 15%, and (d) 45%. Correct activation during the second trial was (a) 3%, (b) 64%, (c) 15%, and (d) 39%. Possible risk of needlestick injury during the second trial was highest with (d). Possibility of deactivation was (a) 0%, (b) 12%, (c) 9%, and (d) 18%. Individual preferences for each system were (a) 11, (b) 17, (c) 5, and (d) 0. The main reason for preference was the comprehensive safety mechanism. CONCLUSION: Significant differences exist between safety mechanisms of winged blood collection needles.

Detection of hypervascular brown tumors on three-phase bone scan.

A patient with hyperparathyroidism secondary to chronic renal failure had multiple bony lesions with increased activity on both immediate static as well as delayed scintiphotos. One lesion in the distal femur was also exceptionally hot on the flow phase. Plain radiographs demonstrated lytic lesions with sclerotic margins and a narrow zone of transition. Open biopsy revealed histology consistent with brown tumor (osteoclastoma).

Intraoperative radiotherapy for pre-irradiated head and neck cancer.

BACKGROUND AND PURPOSE: Radiotherapy of recurrent head and neck tumours is limited in dose due to pre-treatment up to normal tissue tolerance doses. Surgery alone is limited by the problems related to pre-surgery, post-radiation fibrosis, and infiltration of tumours into nerves and vessels too closely to be completely removed. Our aim was to evaluate the possible role of intraoperative radiotherapy (IORT) in such tumours treated with palliative intent. METHODS: In the last 10 years, we performed 113 intraoperative irradiations in a total of 84 pre-irradiated patients with head and neck cancer. The patient data were evaluated with regard to palliative effect, complications of treatment, recurrence and survival after IORT. RESULTS: Palliation of symptoms, as assessed by clinical evaluation, was achieved in 88% of symptomatic patients, often just by removal of large exophytic or exulcerating tumours, with IORT preventing their immediate recurrence after surgery. The complication rate did not exceed that expected after surgery alone. The median survival after IORT was 6.8 months, with a median time to local tumour recurrence or progression of 3.7 months. CONCLUSION: Intraoperative irradiation can be used as a palliative treatment option in pre-treated head and neck tumours with satisfactory results. With large and infiltrating tumours, however, recurrences or tumour progression occur close to the IORT portals, thus rendering this method unsuitable for achieving long-term control in such extended tumours.

After-hours telephone triage and advice in private and nonprivate pediatric populations.

OBJECTIVES: To compare the content of after-hours medical triage and advice calls regarding private practice patients vs nonprivate practice patients and to assess caregiver compliance with advice resulting from these calls. DESIGN: Survey of after-hours medical triage and advice calls during a 2-week period (September 1 through 15, 1996). SETTING: Three private practices (serving approximately 24 000 patients) and 1 urban hospital-based, non-private practice (serving approximately 12 000 patients). SUBJECTS: After-hours medical triage and advice calls from caregivers of patients receiving their primary care in these settings. MAIN OUTCOME MEASURE: Compliance with recommended emergency department (ED) or office visit referrals. RESULTS: A total of 286 calls regarding private practice patients and 377 calls regarding nonprivate practice patients were received (P<.001). Eighty-one calls were referred by the nurse directly to the physician. Fifty-nine private practice patients and 59 nonprivate practice patients were referred to the ED. Caregivers of 94 private practice patients and 132 nonprivate practice patients were given home treatment advice. Appointments to be seen at their primary care source were given for 78 private practice patients and 160 nonprivate practice patients. Non-private practice patients were more likely to be referred for office care (P=.005); private practice patients were more likely to be referred to the ED (P=.01). Compliance with ED referrals was 42% for patients of nonprivate practice and 46% for private practice; for office visit referrals, compliance was 64% for nonprivate practice and 69% private practice patients (P=.71 for compliance with ED referrals and P=.40 for compliance with office referrals). CONCLUSIONS: Compliance with recommended physician encounters was not significantly different (and lower than expected) in both groups of patients. Private practice patients are more likely to be referred to the ED. Calls for nonprivate practice patients are more frequent and these patients are more likely to be referred to their primary care source. This difference may be due to caregivers of patients from nonprivate practices seeking advice for less serious conditions. Physicians should address telephone medicine with caregivers proactively during health maintenance visits.

Anesthesia for the micropremie.

Providing anesthesia for the micropremie involves many considerations beyond what is needed for the full-term neonate. Immaturity of the airway, lungs, cardiovascular system, liver, kidneys, and central nervous system makes the micropremie susceptible to anesthestic complications. Immature respiratory mechanisms and respiratory control increase the risk of apnea, hypoxemia, and hypercapnia intraoperatively as well as postoperatively. Anesthetic drugs depress myocardial contractility and impair baroreflexes in the micropremie to increase the risk of hypotension during anesthesia. Drug metabolism in the micropremie is slow because of the immature liver and kidneys. The micropremie brain requires less drug to achieve the anesthetized state. As a result, administration of the dose and timing of anesthetic drugs differs in the micropremie compared with the full-term neonate. This article describes anesthetic considerations for a few surgical prodedures common in the micropremie.

Symptoms, social stratification and self-responsibility for health in the United States and West Germany.

This study compares the responses of a sample of Americans in Illinois and West Germans in North-Rhine Westphalia on the basis of symptom perception, symptom experience, physician utilization and health-locus-of-control. The hypothesis that as socioeconomic status increases, the more likely the individual is to manifest and behavior favorable toward self-control and acceptance of personal responsibility in health care matters was tested. The hypothesis was supported by the American data, but not the West German. Possible trends in West German society accounting for a significant lack of socioeconomic variance in illness behavior are discussed.

Sensitivity enhancement in ESR/ENDOR spectrometers by use of microwave amplifiers.

The introduction of a low-noise microwave preamplifier in a homodyne ESR spectrometer can increase the signal-to-noise ratio by more than a factor of 10 at low modulation frequencies, and makes it superior to a superheterodyne spectrometer. The performance of this new arrangement has been compared to that of a normal homodyne spectrometer.

Cystic degeneration and calcification of muscle: late sequelae of compartment syndrome.

Cystic degeneration and calcification of the leg are uncommon late sequelae of compartment syndrome. Previously reported cases have all involved the anterior compartment of the leg. We present a 68-year-old man with a mass in the superficial posterior compartment of the leg who presented 37 years after the initial trauma and ischemic myonecrosis. MRI was useful in establishing the diagnosis and early surgical intervention. The mass was excised and closed primarily over a drain. Patient was followed up for 29 months, and there were no secondary infections, chronic sinus formation, or recurrences. Based on our experience and the available literature review, we recommend considering either excision and primary closure, or repeated needle aspiration of the mass. Packing the wound and delayed closure may lead to secondary infection, chronic sinus formation, and lower limb amputation as potential complications.

The paranasal sinuses in CT-imaging: development from birth to age 25.

Available data about the size of the different sinuses to date are derived from anatomical or radiological studies. In order to verify or possibly correct the findings of other authors we evaluated the cranial computed tomography (CT)-images of more than 5600 patients. We measured the sex-linked and age-dependent width and length of the four sinuses for both sides in axial sections. For the first time we have a clear picture of the development of the paranasal sinuses for both sexes from birth until the age of 25 years. Our results confirm general ideas concerning the size of the sinuses. Moreover they provide new details, especially about the first occurrence and the course of development in different stages since we found each sinus already present in 1.5% (frontal sinus) to 94% (ethmoid cells) of the newborn of both sexes. Finally, we can state that the periods of expansion are equal in both sexes (ethmoid cells) or last up to 2 or 3 years longer (frontal sinus) in male patients. In agreement the sinuses of both sexes differ between 5.4% (sphenoid sinus) and 17.1% (frontal sinus) in definitive size with statistically significant differences in later ages. The data about sphenoid sinuses deserve special attention since they show a large variability in size (up to 214% in one direction) as well as in shape.

Efficacy and safety of mometasone furoate nasal spray in the treatment of chronic rhinosinusitis.

INTRODUCTION: This study evaluated the efficacy and safety of mometasone furoate nasal spray (MFNS) in patients with chronic sinusitis. METHODS: In this double-blind, placebocontrolled, multicenter, parallel-group study, 60 patients with persistent sinusitis symptoms were randomized to receive either MFNS 200 µg twice daily or placebo, for 16 weeks (112 days). Eventually, 53 patients terminated the study in regular course. RESULTS: Total Symptom Scores (TSS) in patients receiving MFNS changed by a mean of -7.27 (95% CI -9.71, -4.84), versus -5.35 (95% CI -6.73, -3.96) in the placebo group (P=0.51). MFNS reduced nasal congestion and discharge scores, and improved patients' olfactory function. There were few side effects. Considerably more patients in the MFNS group were satisfied with the treatment than those who had received placebo (P<0.05). Also, more patients would take the medication again in the event of symptoms, compared with those who had taken placebo (P<0.05). Furthermore, the MFNS patients would recommend it to others. CONCLUSION: The positive patient assessment and few side effects are reflected in the efficacy evaluation performed by the physicians. The endoscopic results under MFNS were always numerically more favorable than those under placebo, and the overall difference reached statistical significance (P<0.01). MFNS offers an effective and safe treatment for chronic rhinosinusitis.